We propose to examine the human blood group antigens that mediate differences in susceptibility to disease. Initially, we shall investigate the Duffy blood group and its association with P. vivax malaria (in collaboration with J. Barnwell). We shall explore the relationship between discrete epitopes of this blood group and their ability to support the invasion by malarial merozoites by means of specific monoclonal antibodies (mAbs) of defined specificity. Such mAbs are already available. For the Duffy system the only one thus far encountered is anti-Fy6; for the MN system we have three distinct anti-M specificities and one anti-N, several monomorphic mAbs for glycophorin A and mAbs for the glycophorin A related blood group specificities, En/a and Wr/o. These mAbs have already been shown to inhibit P. vivax (anti-Fy6) with J. Barnwell and P. falciparum (the MN and related specificities) (with M. Perkins, Rockefeller University). We will prepare new mAbs in order to establish an epitope map of the Duffy molecule and verify which of the corresponding mAbs block invasion by P. vivax and P. knowlesi. We will thus obtain a clearer view of the molecular basis for the relationship between the Duffy blood group and the susceptibility of red cells to invasion by P. vivax merozoites. We have also found that hyperimmune anti-P. vivax serum contains antibodies reactive with insolubilized anti-Fy6 mAb, suggesting that the crossreactive specificity recognizes an epitope common to the immunizing agent (P. vivax) and the anti-Fy6 idiotype. Thus, we also propose to prepare anti-idiotypic mAbs for the blood group mAbs most efficient in blocking invasion and assay these mAbs on the appropriate parasite for evidence of suppression at this level.